In patients suffering from treatment-resistant bipolar depression (BP) and with unresponsive chronic pain that is diagnosed as Complex Regional Pain Syndrome (CRPS)have responded to treatment with ketamine. The CRPS patients were treated with a five-day infusion of the drug produced pain relief in 75% of the patients and 67% of the BP responded after a single dose. The objective of the ongoing study is to identify the reasons why some patients respond and other do not, to be able to identify the responders before treatment begins and to individualize treatment to increase response. These initial pharmacokinetic and pharmacodynamic studies of ketamine in CRPS and BP patients are completed. The data indicates that the therapeutic activity of ketamine is due, in part, to (2R,6R)-hydroxynorketamine and dehydronorketamine and the pharmacological activities of the compounds have been investigated. In addition, metabolomic studies have determined that response and non-response to treatment with ketamine in BP patients is related to mitochodrial function. This relationship is under investigation.